A tricyclic compound (I) and a pharmaceutically acceptable salt thereof used in the present invention have been known to possess excellent pharmacological activities such as an immunosuppressive activity and an antimicrobial activity, thereby being useful for treating and preventing rejection against organ-transplantation or tissue-transplantation, graft versus host reaction, various autoimmune diseases and infectious diseases (Japanese Laid-Open Patent Application No. 61(1986)-148181, EP-A-0323042).
Particularly, compounds referred as FR900506(=FK 506 substance), FR900520, FR900523 and FR900525 which belong to the tricyclic compound (I) are produced from genus Streptomyces, in particular, Streptomyces tsukubaensis No. 9993 (Depositary Authority: 1-3, Higashi 1 chome, Yatabe-machi, Tsukuba-gun, Ibaraki-ken, Japan, Fermentation Research Institute Agency of Industrial Science and Technology, Ministry of International Trade and Industry; Date of the Deposit: 5 Oct. 1984; Accession Number: FERM BP-927) or Streptomyces hygroscopicus Subsp. yakushimaensis No. 7238 (Depositary Authority: 1-3, Higashi 1 chome, Yatabe-machi, Tsukuba-gun, Ibaraki-ken, Japan, Fermentation Research Institute Agency of Industrial Science and Technology, Ministry of International Trade and Industry; Date of the Deposit: Jan. 12, 1985; Accession Number: FERM BP-928). In particular, FK 506 substance represented by the following structural formula is a typical compound. ##STR1## Chemical name: 17-allyl-1,14-dihydroxy-12-2-(4-hydroxy-3-methoxycyclohexyl)-1-methylviny l!-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo22.3.1 .0.sup.4,9 !octacos-18-ene-2,3,10,16-tetraone.
It is known that FK 506 substance described above has excellent immunosuppressive activities and is useful for treating and preventing rejection against organ-transplantation and eye diseases.
The Japanese Laid-Open Patent Application No. 1(1989)-157913 teaches that FK 506 substance dissolved in ethanol is effective against inflammatory inhibition and FK 506 substance can be formulated in the form of a lotion, gel and cream. However, there is no disclosure in the publication about specific preparations of the lotion, gel and cream.
Also, Japanese Laid-Open Patent Application No. 5(1993)-17481 discloses ointment comprising a tricyclic compound (I) or a pharmaceutically acceptable salt thereof, a solubilizing and/or absorption-promoting agent in an amount at least sufficient to dissolve the tricyclic compound or its salt, and an ointment base.
Ointment or the like has been mainly used for treating skin disease. However, various types of preparation are demanded depending on the part to be applied. For example, in case of application to the head skin, it is preferred that less amount of the formulation remains after the application.